Elucidation of the biology of initiation and emergence of epithelial neoplasms, as illustrated by mammary and cervicovaginal tumorigenesis, is the overall objective of this proposal. Our research plan combines a variety of in vivo and in vitro experimental approaches to these problems, utilizing mouse and rat model systems and, in some cases, human cells. Experiments are designed to analyzed the cellular composition of the mammary gland and its tumors and to examine the roles of hormones, viruses, chemical agents, and cellular and host factors in the growth of normal and neoplastic cells, including metastatic tumors. Cervicovaginal studies with the mouse model will focus on dysplasias induced by perinatal steroid administration and their subsequent transformation into carcinomas in host environments modified by hormonal and immunological manipulations. Antigenicity and the metastatic behavior of these carcinomas will also be analyzed. We expect that our studies on these two systems will generate models that can be used for both in vitro and in vivo analyses of other epithelial neoplasms.